The present invention relates to a dedicated small scale system suitable for biomedical applications which measures the concentration of tritium in a sample containing other species of hydrogen.
The use of radioactive isotopes in various molecules as labels to track metabolic processes is well known in the arts of medicine and the biosciences. The samples available for analysis in such testing and research are typically very small, in the range of 10 micrograms (ug) to 1 milligram (mg). Obtaining a measurement with the required accuracy from such a small sample is often very difficult. Attempts to measure the concentration of the radioactive isotope directly by decay counting may not provide the required accuracy. Unfortunately, decay analysis techniques from small samples require the use of an isotope with a relatively rapid rate of decay for proper operation.
The heretofore required use of short half-life isotopes, i.e., isotopes which relatively rapidly decay to a non-radioactive state, has a variety of undesirable consequences. For obvious reasons, the isotope has a short shelf-life, making it difficult to maintain in stock and inconvenient for routine test procedures. Any use of the isotope must account for its state of decay at the outset of the test, and the accuracy of the analysis is limited both by the difficulty in accurately measuring concentrations by decay techniques and the instability of the starting material. Such isotopes often cannot be used for long term tests, and are limited to tests which require only a short time to complete. The radioactivity may make the isotope potentially hazardous to the user, and it is difficult to avoid contamination of the equipment. The limitation on half-life means that isotopes which might otherwise be desirable cannot be used because their half-life is unacceptably long. Finally, the short half-life of the isotope often means that it must be attached to the sample shortly before the initiation of the test, typically requiring surface bonding techniques which do not always adequately bond the isotope to the sample.
In the geosciences, the use of radioactive isotopes with a relatively long half-life for analysis and testing is well known. The samples available in the geosciences are typically large relative to the samples available in medicine and the biosciences, and techniques exist for directly detecting the concentration of the isotopes with the necessary accuracy without relying on an analysis of their rate of decay. One such technique is generally known as accelerator mass spectrometry (AMS), and involves the acceleration of the radioactive particle in ionized form, measuring its concentration in the sample by deflecting the accelerated beam into components based on relative mass, and comparing the concentrations in the respective beams.
Recent research involving the application of AMS to the biomedical sciences, performed by the assignee of this application, is reported in "Application of AMS to the Biomedical Sciences" and "Accelerator Mass Spectrometry in the Biomedical Sciences: Applications in Low-Exposure Biomedical and Environmental Dosimetry", presented at the Fifth International Conference on Accelerator Mass Spectrometry held in Paris, France in April., 1990. Those papers discuss the potential uses of AMS in biomedicine, and the radioisotopes, particularly carbon 14, which may be useful. However, those papers do not provide an explanation of the actual techniques used to perform the spectrographic analysis.
One isotope which has found various applications in the biomedical sciences as well as other fields is tritium, a species of hydrogen having an atomic mass of 3 (i.e., one proton and two neutrons). Tritium exists naturally, and it can also be produced artificially. Tritium has practical uses as a label for biomedical substances of interest. Tritium can be detected using decay (typically beta) techniques, but only with sample sizes or tritium concentrations which are often too large to be practical for many biomedical or clinical purposes.
The direct detection of tritium using AMS in sample sizes sufficiently small for biomedical research has been the subject of several recent studies. For example, in "Detection of Tritium Using Accelerator Mass Spectrometry", King et al., Nuclear Instruments and Methods in Physics Research B29 (1987) 14, a cyclotron is used to accelerate the tritium, an aluminum shield blocks .sup.3 He and other undesired particles, and the remaining particles pass through a .DELTA.E-E detector. A tandem accelerator is used in "Tritium Measurements with a Tandem Accelerator", Middleton et al., Nuclear Instruments and Methods in Physics Research B47 (1990) 409. A Van de Graaff accelerator is used in "Determination of Tritium using a Small Van de Graaff Accelerator", Songsheng et al., Nuclear Instruments and Methods in Physics Research B5 (1984) 226. However, all post tritium AMS techniques require relatively large, complex devices which are impractical for most biomedical applications.